Endoplasmic reticulum stress plays critical role in brain damage after chronic intermittent hypoxia in growing rats

Cai, Xiaohong; Li, Xiucui; Jin, Shudong; Liang, Dongshi; Wen, Zhengwang; Cao, Hongchao; Mei, Hongfang; Wang, Ying; Lin, Zhongdong; Wang, Liangxing

doi:10.1016/j.expneurol.2014.04.029

Cited by 76 publications

(43 citation statements)

References 35 publications

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“…An extensive body of work using rodent models has demonstrated that chronic exposures to intermittent hypoxia during the rest period, in the absence of significant sleep fragmentation, is accompanied by neurodegenerative changes, increased oxidative stress and inflammation, and impaired spatial learning in the Morris water maze [15][16][17][18][19][20][21][22][23][24], and that genetic or pharmacological manipulations of oxidative stress pathways attenuated intermittent hypoxia-induced deficits [25][26][27]. However, the recovery from such intermittent hypoxia-induced central nervous system structural and functional alterations has not been systematically investigated.…”

Section: Introductionmentioning

confidence: 99%

Temporal trajectories of novel object recognition performance in mice exposed to intermittent hypoxia

et al. 2017

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Intermittent hypoxia is one of the major perturbations of sleep-disordered breathing and has been causally implicated in neurocognitive deficits. However, the reversibility of such deficits is unclear.Male C57BL/6J mice were exposed to either intermittent hypoxia or room air for 3-240 days, and then half were randomly selected and allowed to recover in normoxic conditions for the same duration of the previous exposure. A novel object recognition (NOR) test was performed.NOR performance was stable over time in room air. Intermittent hypoxia induced significant reductions in recognition index that progressed over the first 45 days and stabilised thereafter. Normoxic recovery of recognition index was essentially complete and indistinguishable from room air in mice exposed to shorter intermittent hypoxia times (<90 days). However, significant residual deficits emerged after normoxic recovery following prolonged intermittent hypoxia exposures (p<0.01). In addition, gradual attenuation of the magnitude of recovery in recognition index occurred with increasingly longer intermittent hypoxia exposures (MANOVA p<0.0001).Intermittent hypoxia during the resting period reduces NOR performance in a time-dependent fashion. Reversal of NOR performance deficits is unlikely after prolonged intermittent hypoxia duration. These findings suggest that early recognition of sleep apnoea and effective treatment are critical for restoration of the adverse cognitive effects of the disease.

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Section: Introductionmentioning

confidence: 99%

Temporal trajectories of novel object recognition performance in mice exposed to intermittent hypoxia

et al. 2017

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“…Physiologically, apnea and hypopnea in OSAHS patients present symptoms of hypoxia, hypercapnia, and sleep disorders and may cause neurocognitive impairment and memory loss, if untreated. [21][22][23][24] The exact mechanisms linked with OSAHS and growth retardation remain unknown. Delays in bone age in children are commonly accompanied by a series of symptoms, such as the deficiency of GH, chronic illness, malnutrition, and hypothyroidism.…”

Section: Discussionmentioning

confidence: 99%

Bone Age and Serum Osteocalcin Levels in Children With Obstructive Sleep Apnea Hypopnea Syndrome Before and After Adenotonsillectomy

Feng

Tian

Zhang³

et al. 2017

American Journal of Therapeutics

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Our aim was to study the changes in bone age and serum osteocalcin levels before and after adenotonsillectomy (AT) in children with obstructive sleep apnea hypopnea syndrome (OSAHS). A total of 58 OSAHS children (37 males and 21 females) with the mean age of 6.68 ± 1.11 years were enrolled and assessed by x-ray-based bone age estimation and enzyme-linked immunosorbent assay-based measurement of serum osteocalcin levels, before surgery and 6 months after AT. SPSS 19.0 software was used for statistical analysis. Our results revealed that bone age and serum osteocalcin levels in OSAHS patients were significantly lower than normal controls before AT (P < 0.05). Within 6 months after surgery, the bone age and the serum osteocalcin levels were significantly elevated in OSAHS patients (P < 0.05), compared with those before surgery. Serum osteocalcin levels and bone age are negatively correlated with apnea-hypopnea index, oxygen desaturation index, the percentage of the total recorded time spent below 90% oxygen saturation, and Epworth sleepiness scale scores (all P < 0.05). Our findings suggested that bone age and serum osteocalcin levels may be correlated with the development of OSAHS in children. AT may improve bone age and serum osteocalcin levels in OSAHS children.

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“…Salubrinal has neuroprotective effects in animal models of CNS injury, such as a rat brain excitotoxicity [43], cerebral ischemia/reperfusion [44, 45], and chronic intermittent hypoxia [46]. It is neuroprotective also in mouse models of sleep apnea [47], traumatic brain injury [48, 49], and cortical stab injury [50].…”

Section: Cns Injury Therapeutics Based On the Integrated Stress Rementioning

confidence: 99%

“…The release of PDGF-B in the proximity of the lesion site might help to close the injury, accelerating BBB integrity restoration [50]. Moreover, in a rat model of global cerebral ischemia, salubrinal reduced the levels of matrix metalloprotease 9 (MMP-9), as well as of the injury-induced cell adhesion molecules ICAM-1 and VCAM-1 [46]. MMP-9 is a typical marker of BBB impairment [61, 62] and both ICAM-1 and VCAM-1 are involved in leukocyte migration into the injured CNS [63].…”

Section: Cns Injury Therapeutics Based On the Integrated Stress Rementioning

confidence: 99%

Integrated Stress Response as a Therapeutic Target for CNS Injuries

Romero‐Ramírez

Nieto–Sampedro

Barreda-Manso

2017

BioMed Research International

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Central nervous system (CNS) injuries, caused by cerebrovascular pathologies or mechanical contusions (e.g., traumatic brain injury, TBI) comprise a diverse group of disorders that share the activation of the integrated stress response (ISR). This pathway is an innate protective mechanism, with encouraging potential as therapeutic target for CNS injury repair. In this review, we will focus on the progress in understanding the role of the ISR and we will discuss the effects of various small molecules that target the ISR on different animal models of CNS injury.

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Endoplasmic reticulum stress plays critical role in brain damage after chronic intermittent hypoxia in growing rats

Cited by 76 publications

References 35 publications

Temporal trajectories of novel object recognition performance in mice exposed to intermittent hypoxia

Temporal trajectories of novel object recognition performance in mice exposed to intermittent hypoxia

Bone Age and Serum Osteocalcin Levels in Children With Obstructive Sleep Apnea Hypopnea Syndrome Before and After Adenotonsillectomy

Integrated Stress Response as a Therapeutic Target for CNS Injuries

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